The transmissible spongiform encephalopathies (TSEs) consist of several invariably fatal degenerative diseases of the nervous system of humans and other mammals. These diseases are normally relatively species- specific but the recent epizootic of bovine spongiform encephalopathy (BSE) in the United Kingdom and the coincidental appearance of a variant of the spongiform disease, Creutzfeldt-Jakob disease (CJD) in humans, has led to speculation that BSE has crossed the species barrier and that a human epidemic is incubating the British and other populations. To confirm the diagnosis of TSE in humans or animals, it is necessary to demonstrate the presence of the abnormal isoform of the prion protein (PrP) known as PrPSc. Evidence has been presented by British investigators suggesting that PrPSc from various TSEs exhibit unique and reproducible blot profiles compared to others. It has furthermore been suggested that these reproducible characteristics prermit differentiation between sporadic CJD, iatrogenic CJD, and new variant CJD particularly after deglycosolation of the protein. Further findings strongly suggest a link between the human veterinary diseases. We extract PrPSc from different areas of the brain of a sporadic CJD case and from brains of hamsters infected with known strain of sheep scrapie. Western blot profiles clearly differed between the CJD material and the scrapie samples. Different areas of the human brain exhibited different concentrations of PrPSc with highest levels observed in parietal lobe and thalamus. Samples from the parietal lobe and basal ganglia show four bands at slightly lower molecular weights than other areas of the brain which exhibited profiles of varying intensity with only three bands suggesting that variation in PrPSc composition as determined by Western immunoblot may occur in different areas of the brain of a single individual. Investigations are underway to determine the significance of these differences and whether they persist after deglycosolation.